Comparar las concentraciones de la vermicomposta en diferentes

It is still unknown whether Candida is an opportunistic invader or initiator of oral cancer (Arendorf et al, 1983; Holmstrup and Besserman, 1983) however oral dysplastic lesions with candidal infection have a greater risk of malignant transformation (Johnson, 1991).

1.3.5 Diet and Nutrition

Nutritional deficiency is considered to produce atrophy of mucous membranes and it is possible that this makes them more permeable to local carcinogens. The importance of vitamin A and C has been highlighted by Franceschi et al (1990). Use of 13- carotene and retinoids has been used to reverse premalignant leukoplakia (Stich et al,

1988). Gridley et al (1992) found that users of supplements of vitamins A, B, C and E were at lower risk of oral and oro pharyngeal cancer (after controlling for other risk factors). After adjusting for all the vitamin supplements it was found that vitamin E was the only one associated with a significantly reduced cancer risk. The effect of iron deficiency is discussed in another section (sideropenic dysphagia). Hebert et al

(1993) found, after accounting for other aetiological factors, a protective effect against oral cancer from milk or dairy products and cabbage consumption but an increased risk from vegetable oil and excess animal fat consumption. La Vecchia et

<3/(1991) found that the strongest protection from oral cancer was from frequent fruit consumption.

1.3.6 Mouthrinses and dental hygiene

Winn et al (1991) demonstrated a significant increase in oral and oro-pharyngeal cancer associated with regular use of a mouthwash. This risk was increased by 40% in males and 60% in females after adjustment for smoking and alcohol intake. The risk appeared to be in proportion to dose, frequency of use and the alcohol concentration of the mouthwash. Llewelyn (1994) expressed his concern at deregulation of mouthwashes in the United Kingdom, in that continual use for plaque removal may increase the risk of oral carcinoma, and called for warning labels on these products. A recent study by Maier et al (1993) demonstrated a relationship between poor oral hygiene and an increased risk of oral cancer in a matched case control study. Poor oral hygiene is related to social status and oral cancer is more common in social classes IV and V, so this finding is probably coincidental since cancers rarely arise in areas of oral sepsis (Cancer Research Campaign, 1993). 1.4 Screening

1.4.1 Principles o f screening

Screening as a method of preventive medicine arose from the concept that treatment of diseases early in their development offered the best chance o f cure or prevention of progression. Screening is defined as the application of a test or tests to people who are apparently free of the disease in question in order to sort out those who probably have the disease from those who probably do not. A screening test is not intended to

be diagnostic. Persons with positive or suspicious findings must be referred to their physicians for diagnosis and necessary treatment (Wilson & Jungner, 1968). There are several situations in which individuals are screened:

1. Early diagnosis of a disease or ’pre-symptomatic screening’. The objective of this type of screening is to detect a disease (usually a cancer) more frequently at a pre-invasive phase or at an earlier stage of invasive disease than is usual in clinical practice (Shapiro, 1992). This should therefore interrupt the natural history of the disease and prevent progression to advanced disease and death (Chamberlain, 1993). 2 Protection of the public from infectious diseases, for example by the routine screening of immigrants.

3 Prior to entry into an organisation, for example train drivers with eye defects. 4 Protection of a work force, for example, protection against radiation in hospital radiographers by monitoring radiation badges.

5 Life insurance, by assessing those individuals who are more at risk of a disease by medical screening.

1.4.2 History o f screening.

examination of children of school age and in routine post-natal care. Screening for endemic industrial diseases such as silicosis by chest x rays was also implemented around that time. Screening for pulmonary tuberculosis was introduced in 1943 and enabled treatment to be commenced at an earlier stage as well as removing the affected person from the community.

Screening for conununicable disease became less important with the widespread use of antibiotics and increased medical knowledge, so that more emphasis was placed on non-communicable diseases such as cancer and heart disease. Screening for phenylketonuria was developed within the NHS in the mid 1950s, cervical cancer screening in the 1960s and trials for breast cancer screening commenced in the mid 1980s. The success of a screening programme is judged in terms of its cost- effectiveness and overall reduction in mortality and morbidity by prevention of the disease. For example, screening for phenylketonuria although uncommon (one in

2 0 ,0 0 0) was found to be cost effective since the cost of prevention was less than the

cost of treating the established disease (Butler, 1993).

Screening for cervical cancer has been widely established throughout the United Kingdom and although overall time trends in mortality did not initially appear to be effected by screening, detailed analyses showed that ’in the absence o f screening, an increase in mortality would have occurred’ (Hakama, 1990). They stated that screening in the United Kingdom may have resulted in ’a 20-30 per cent reduction in risk of and mortality from cervical cancer’. The main problem is that 60% of women who develop cervical cancer have never been screened despite financial incentives by

the Government (Williams, 1992). Hakama (1990) stated that the reduction in risk is closely related to the organisation of the programme. This is certainly true in Finland where a population based, well organised programme with a wide target age range was established which resulted in a reduction of 60% in cervical cancer incidence. Breast cancer screening has been examined after 10 years of follow-up and it was found that although the reduction in mortality was 14-21% in those screened, the results were not statistically significant. In the screened population the number of patients with locally advanced disease and metastasis was found to be much lower (Alexander et al, 1994).

Targeting cancer may provide benefit to the whole population in terms o f reduced health care costs but it is more likely that the benefit is at the individual level in terms of increasing that individual’s quantity and quality of life. In a review of screening Holland (1974) gave three reasons for screening; for preventing or treating a disease and equally important but often overlooked alleviating a disease which is beyond cure or prevention, for example, providing glasses or hearing aids.

1.4.3 Ethical and psychological problems associated with screening

It is generally accepted that if a screening programme is implemented there is an ethical obligation to ensure that it does more good than harm to the participant and that the adverse psychological effects are negligible (Flynn, 1991; Austoker, 1994b). For example the lung cancer screening programme in the United Kingdom was

abandoned since it failed to show any benefits between the screened and unscreened populations in terms of cumulative mortality rates (Fontana, 1985).

Although the theoretical ideal of screening is justifiably beneficial there have been criticisms levelled from other health professionals (Mant & Fowler, 1990) who claim that ’screening has the potential to do more harm than good’. Marteau (1989) demonstrated high levels of anxiety in patients participating in screening programmes. She suggested that screening-related anxiety could be reduced by explaining why a particular patient had been selected and the benefits to that individual of being screened. Edwards and Hall (1992) stated that an individual should be able to provide informed consent prior to being screened.

Marteau (1990) also recommended that informing the screened individual of their screening result would reduce any adverse psychological effects. Lerman and Rimer (1993) found that the distress associated with receiving abnormal cancer screening results may interfere with participation in subsequent screening and diagnostic follow- up. They concluded that no screening programme should be initiated without planning how the communication of an abnormal result and its follow-up were to be dealt with. However a study, in which the psychological reactions to a melanoma screening programme were measured, showed no increase in psychosomatic problems, anxiety or false sense of security, but an increased subjective susceptibility to melanoma was demonstrated (Brandberg et al, 1993). In a study to investigate the adverse effects of mammographie screening the most significant effect was in those subjects who were recalled for a suspicious lesion and the authors called for accurate reading of all

mammographs in order to reduce recall for false positives. However no long-term effects were found (Cockburn et al, 1994).

1.4.4 Screening fo r cancer

’Screening is now regarded as a cost-effective and clinically useful approach for the early diagnosis of several malignancies especially such diseases as breast and cervical cancer.’ (Miller et al, 1991).

Breast cancer screening

Mammography is the most effective method of screening for breast cancer. An interval of 1-3 years is recommended and has been found to substantially reduce breast cancer mortality in women aged 50 to 70 years of age. It has been found to be cost-effective. In women less than 50 there appears to be minimal benefit. The aim of the British Government is to reduce the rate of breast cancer deaths among women invited for screening by at least 25% (from 95.1 per 100,000 to 71.3 per 100,000) by the year 2000 (Department of Health, 1992).

Cervical cancer

Screening for cancer of the cervix by cytology has been found to be effective in reducing the incidence and mortality of the disease (Hakama, 1990; Parkin et al,

women entering at 25 years of age, with a screening interval of 3-5 years up to the age of 60. The aim of the British Government is to reduce the incidence of invasive cervical cancer by at least 20% (from 15 per 100,000 population to no more than 12 per 100,000) by the year 2000 (Department of Health, 1992).

Colorectal cancer

It is not yet determined whether removal of adenomas (possible precursors to colorectal cancer) has an effect on cancer incidence and mortality. Much work is being done in the field of faecal occult blood tests to assess their sensitivity and specificity. Targeting of high risk individuals (close relatives) is generally thought to be effective.

Ovarian cancer

There is little data on the effect of screening for ovarian cancer on mortality. However the five year survival rate is greater than 95 % in patients whose cancer is limited to the ovary (Dembo et al, 1990) compared to approximately 10% in advanced disease (Kottmeier, 1982). Unfortunately like oral cancer the majority of patients (60%) present with advanced disease. There is a concerted effort to develop a screening system to diagnose ovarian cancer at a pre-clinical stage thus decreasing incidence and mortality.

Malignant melanoma

Screening for malignant melanoma is still at an early stage of development although it is gaining in momentum in countries such as Australia and New Zealand. When melanomas are detected at an early stage there is a high cure rate. The incidence is rising in the United Kingdom and there is a call for increased public awareness. The aim of the British Government is to halt the year on year increase of skin cancer by the year 2005 (Department of Health, 1992).

Prostate cancer

Screening is at a developmental stage since there are arguments about the sensitivity and specificity of the tests available (Denis et al, 1995). Another problem is that it is a disease which effects the elderly and therefore may not be cost effective, however much research is needed to evaluate this fully.

1.5 Screening fo r oral cancer

A renewed interest in screening for oral cancer has been expressed in recent years, by the dental media and profession since it may be a simple and effective method of controlling a disease of high morbidity and mortality. Maloof (1984) listed several reasons why oral cancer is a lesion which is ideal for screening. The main consideration is that it is easy to detect at all stages of development and that early diagnosis results in simple treatment, better cosmetics and survival. In 1991, a UK

working group was organised to assess the possibility o f screening for oral cancer and this resulted in a publication outlining the overall advantages and disadvantages (Speight et al, 1993). There have been several communications in the dental media highlighting the year on year increase in new registrations of oral cancer (Boyle et al, 1993; Renson, 1990; Kindle and Nally, 1991) and concern has been expressed at the large percentage of patients who present late for treatment. Hutchison (1994) lists the reasons for late referral as lack of knowledge by patients and professionals and the increased charges for dental treatment which deter people in high risk groups from attending for regular examinations.

Many groups have measured the prevalence of oral mucosal disease (Hogewind and van der Waal, 1988; Jorge et al, 1991; Ikeda et al„ 1995a; Dombi et al, 1994; Kleinmann et al, 1993) but few studies have investigated screening for oral cancer. Few of these have assessed the validity of screening with some exceptions (Ikeda et al, 1988, Wamakulasuriya and Pindborg, 1990). A need exists therefore to assess screening in terms of its effectiveness and accuracy in detecting oral cancer at an earlier stage than would occur in normal clinical practice.

1.5.1 Screening tests fo r oral cancer

There are several methods to examine the mouth for oral cancer or precancer. It is important that the screening test is simple, cheap and acceptable. The three main methods described in the literature are discussed below. There are more advances being made in the field of genetic testing but this is still very developmental.

Visual examination

This method of screening for oral cancer is simple and involves a systematic examination of the oral soft tissues (Mock, 1985; British Postgraduate Medical Federation, 1991). The following procedure is recommended by the World Health Organisation (1980) for a thorough methodical examination of the mouth, using two mouth mirrors and a good light source.

Lips : examined when open and closed. Any variation in texture, colour or irregularities in the vermilion border are noted.

Lower and upper labial sulci and mucosa: examined with the mouth partially open noting any swellings or changes in colour of the oral mucosa.

Labial commissures, buccal mucosa, buccal sulci (upper and lower): the mouth mirrors are used as retractors and the mouth is wide open. The entire buccal mucosa is examined from the commissures to the anterior pillar of the fauces. Any changes in colour or mobility are noted and it must be ensured that the mirrors do not cover the commissures when retracting the buccal mucosa

Alveolar ridges and gingiva: are checked both lingually and buccally.

Tongue: is examined initially at rest with the mouth partially open. The dorsum of the tongue is examined for any swelling, ulceration or changes in colour or texture

o f the surface and papillae. The tongue is then protruded and any abnormal mobility is noted. The ventral surface is then examined similarly.

Floor of mouth: with the tongue elevated this area is examined for any changes in colour or presence of ulcers.

Hard and soft palate: with the mouth wide open and the tongue depressed to allow examination of the hard palate and soft palate.

The facial tissues should also be examined and the sub-mandibular and cervical nodes palpated.

This technique should take about 3 minutes to complete. Roed-Petersen and Renstrup (1969) designed a map of the oral mucosa to record any abnormalities detected by clinical examination. In other studies the examiners indicated the area of abnormality on a checklist (Downer et al, 1995).

Toluidine Blue Dye

Toluidine Blue is a member of the thiazine group of metachromatic dyes, which is soluble in both water and alcohol (Strong et al, 1968). It primarily stains nucleic acids which are present in large quantities in malignant, pre-malignant, ulcerated and inflamed tissues. The technique was initially described by Rickart (1963) and has been widely used to detect neoplastic areas on the cervix.

Several groups (Shedd et al, 1967; Myers, 1970; Mashberg, 1984) have suggested that toluidine blue can be used as an adjunct to oral cancer screening because of its ability to stain potentially malignant areas of the mouth. The toluidine blue dye can either be applied directly using a cotton wool tip to the suspicious area or used as a rinse. Mashberg (1984) quotes a sensitivity of 89.9% and specificity of 90.8% using a technique which involves two applications of the dye 10 to 14 days apart. Between applications, all possible irritants to the oral mucosa are removed to reduce false positives due to traumatic lesions. However another study (Miller et at, 1988) staining malignant and premalignant lesions in the hamster cheek pouch reported a false negative rate of 27.8% in detecting carcinomas and 95.2% in detecting carcinoma in situ and dysplasia.

It is possible that toluidine blue dye does have a place in detecting malignant and premalignant lesions of the mouth in patients following radiotherapy to detect possible recurrence or field changes but it is not considered to be a substitute for biopsy or close visual examination (Myers, 1970).

Oral exfoliative cytology

Oral exfoliative cytology is a method of obtaining a sample of epithelial cells either by scraping or rinsing the oral mucosa. Since Cahn (1965) found that malignant epithelial cells are less cohesive that normal epithelial cells, the presence of disease is easy to determine since malignant cells will be abundant in the exfoliate. Folsom

cytological scraping of any lesions detected on dental examination and concluded that although useful as an adjunct for diagnosis its limitations should be acknowledged. However Nicholls et al (1991) found that the sensitivity and specificity for brush cytology was high with low inter-observer variability and concluded that it may have a place as an aid to identifying clinically unsuspected cancers or precancers especially those with field cancerization. Vaillant et al (1994) demonstrated a 96% reliability with cytological smears. Ogden et al (1994) have developed sophisticated analysis techniques in analysing smears achieving a sensitivity of 0.70 (DNA profile) and 0.90 (keratin markers) and it is possible that it has a place in reviewing patients for field changes or possible secondary oral cancers. However the widespread opinion is that oral exfoliative cytology is unreliable since dysplastic epithelium is rarely superficial enough to provide an adequate cytological scrape (Scully, 1993).

1.5.2 Criteria fo r screening

Prior to the implementation of a screening programme several accepted criteria should be met (Wilson & Jungner, 1968). Interestingly these criteria fail to take into account any changes in quality of life which may arise from screening (Denis et al, 1995). The criteria are listed below and the arguments for oral cancer discussed.

The condition sought should be an important health problem.

The disease must be measured in terms of importance to both the individual and the community. Although oral cancer is a relatively uncommon disease in the United

K ingdom , w ith an incidence rate o f 4 per 100,000 and 2,337 new registrations